Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar;25(3):184-195.
doi: 10.1038/s41576-023-00656-z. Epub 2023 Oct 20.

Inborn errors of immunity: an expanding universe of disease and genetic architecture

Yemsratch T Akalu  1 , Dusan Bogunovic  2
Affiliations
Review

Inborn errors of immunity: an expanding universe of disease and genetic architecture

Yemsratch T Akalu et al. Nat Rev Genet. 2024 Mar.

Abstract

Inborn errors of immunity (IEIs) are generally considered to be rare monogenic disorders of the immune system that cause immunodeficiency, autoinflammation, autoimmunity, allergy and/or cancer. Here, we discuss evidence that IEIs need not be rare disorders or exclusively affect the immune system. Namely, an increasing number of patients with IEIs present with severe dysregulations of the central nervous, digestive, renal or pulmonary systems. Current challenges in the diagnosis of IEIs that result from the segregated practice of specialized medicine could thus be mitigated, in part, by immunogenetic approaches. Starting with a brief historical overview of IEIs, we then discuss the technological advances that are facilitating the immunogenetic study of IEIs, progress in understanding disease penetrance in IEIs, the expanding universe of IEIs affecting distal organ systems and the future of genetic, biochemical and medical discoveries in this field.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Tangye, S. G. et al. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 40, 24–64 (2020). - PubMed - PMC
    1. Beck, D. B. et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 383, 2628–2638 (2020). - PubMed - PMC
    1. Bousfiha, A. et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. J. Clin. Immunol. 42, 1508–1520 (2022). - PubMed
    1. Tangye, S. G. et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 42, 1473–1507 (2022). This work presents the most up-to-date report of the classification of IEIs and their associated features. - PubMed - PMC
    1. Fischer, A. Gene therapy for inborn errors of immunity: past, present and future. Nat. Rev. Immunol. 23, 397–408 (2023). This article reviews the development of gene therapies for IEIs and discusses the next steps for the field. - PubMed

LinkOut - more resources